Johnson Ashley R, Caudill Cassie L, Tumbleston John R, Bloomquist Cameron J, Moga Katherine A, Ermoshkin Alexander, Shirvanyants David, Mecham Sue J, Luft J Christopher, DeSimone Joseph M
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, United States of America.
Department of Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27510, United States of America.
PLoS One. 2016 Sep 8;11(9):e0162518. doi: 10.1371/journal.pone.0162518. eCollection 2016.
Microneedles, arrays of micron-sized needles that painlessly puncture the skin, enable transdermal delivery of medications that are difficult to deliver using more traditional routes. Many important design parameters, such as microneedle size, shape, spacing, and composition, are known to influence efficacy, but are notoriously difficult to alter due to the complex nature of microfabrication techniques. Herein, we utilize a novel additive manufacturing ("3D printing") technique called Continuous Liquid Interface Production (CLIP) to rapidly prototype sharp microneedles with tuneable geometries (size, shape, aspect ratio, spacing). This technology allows for mold-independent, one-step manufacturing of microneedle arrays of virtually any design in less than 10 minutes per patch. Square pyramidal CLIP microneedles composed of trimethylolpropane triacrylate, polyacrylic acid and photopolymerizable derivatives of polyethylene glycol and polycaprolactone were fabricated to demonstrate the range of materials that can be utilized within this platform for encapsulating and controlling the release of therapeutics. These CLIP microneedles effectively pierced murine skin ex vivo and released the fluorescent drug surrogate rhodamine.
微针是由微米级针头组成的阵列,能够无痛穿透皮肤,实现经皮给药,而许多药物采用传统给药途径很难实现经皮给药。已知许多重要的设计参数,如微针的尺寸、形状、间距和组成,都会影响疗效,但由于微制造技术的复杂性,这些参数很难改变。在此,我们利用一种名为连续液体界面生产(CLIP)的新型增材制造(“3D打印”)技术,快速制作出具有可调几何形状(尺寸、形状、纵横比、间距)的尖锐微针。该技术无需模具,每片微针阵列只需不到10分钟即可一步制造出几乎任何设计的微针阵列。制作了由三羟甲基丙烷三丙烯酸酯、聚丙烯酸以及聚乙二醇和聚己内酯的可光聚合衍生物组成的方形金字塔形CLIP微针,以展示该平台可用于封装和控制治疗药物释放的材料范围。这些CLIP微针在体外有效刺穿了小鼠皮肤,并释放出荧光药物替代物罗丹明。